Increase from low to moderate, but not high, caffeinated coffee consumption is associated with favorable changes in body fat.

BACKGROUND & AIMS: Higher consumption of coffee and caffeine has been linked to less weight gain and lower body mass index in prospective cohort studies. The aim of the study was to longitudinally assess the association of changes in coffee and caffeine intake with changes in fat tissue, in particular, visceral adipose tissue (VAT) using dual x-ray absorptiometry (DXA). METHODS: In the setting of a large, randomized trial of Mediterranean diet and physical activity intervention, we evaluated 1483 participants with metabolic syndrome (MetS). Repeated measurements of coffee consumption from validated food frequency questionnaires (FFQ) and DXA measurements of adipose tissue were collected at baseline, 6 months, 12 months and 3 years of follow-up. DXA-derived measurements of total and regional adipose tissue expressed as % of total body weight were transformed into sex-specific z-scores. Linear multilevel mixed-effect models were used to investigate the relationship between changes in coffee consumption and corresponding concurrent changes in fat tissue during a 3-year follow-up. RESULTS: After adjustment for intervention group, and other potential confounders, an increase in caffeinated coffee consumption from no or infrequent consumption (≤3 cups/month) to moderate consumption (1-7 cups/week) was associated with reductions in total body fat (Δ z-score: -0.06; 95% CI: -0.11 to -0.02), trunk fat (Δ z-score: -0.07; 95% CI: -0.12 to -0.02), and VAT (Δ z-score: -0.07; 95% CI: -0.13 to -0.01). Neither changes from no or infrequent consumption to high levels of caffeinated coffee consumption (>1 cup/day) nor any changes in decaffeinated coffee consumption showed significant associations with changes in DXA measures. CONCLUSIONS: Moderate changes in the consumption of caffeinated coffee, but not changes to high consumption, were associated with reductions in total body fat, trunk fat and VAT in a Mediterranean cohort with MetS. Decaffeinated coffee was not linked to adiposity indicators. Moderate consumption of caffeinated coffee may be part of a weight management strategy. TRIAL REGISTRATION: The trial was registered at the International Standard Randomized Controlled Trial (ISRCTN: http://www.isrctn.com/ISRCTN89898870) with number 89898870 and registration date of 24 July 2014, retrospectively registered.

Allium vegetables intake and the risk of gastric cancer in the Stomach cancer Pooling (StoP) Project.

BACKGROUND: The role of allium vegetables on gastric cancer (GC) risk remains unclear. METHODS: We evaluated whether higher intakes of allium vegetables reduce GC risk using individual participant data from 17 studies participating in the "Stomach cancer Pooling (StoP) Project", including 6097 GC cases and 13,017 controls. Study-specific odds ratios (ORs) were pooled using a two-stage modelling approach. RESULTS: Total allium vegetables intake was inversely associated with GC risk. The pooled OR for the highest versus the lowest study-specific tertile of consumption was 0.71 (95% confidence interval, CI, 0.56-0.90), with substantial heterogeneity across studies (I2 > 50%). Pooled ORs for high versus low consumption were 0.69 (95% CI, 0.55-0.86) for onions and 0.83 (95% CI, 0.75-0.93) for garlic. The inverse association with allium vegetables was evident in Asian (OR 0.50, 95% CI, 0.29-0.86) but not European (OR 0.96, 95% CI, 0.81-1.13) and American (OR 0.66, 95% CI, 0.39-1.11) studies. Results were consistent across all other strata. CONCLUSIONS: In a worldwide consortium of epidemiological studies, we found an inverse association between allium vegetables and GC, with a stronger association seen in Asian studies. The heterogeneity of results across geographic regions and possible residual confounding suggest caution in results interpretation.

Coffee consumption and gastric cancer: a pooled analysis from the Stomach cancer Pooling Project consortium.

OBJECTIVE: This study aimed to evaluate and quantify the relationship between coffee and gastric cancer using a uniquely large dataset from an international consortium of observational studies on gastric cancer, including data from 18 studies, for a total of 8198 cases and 21 419 controls. METHODS: A two-stage approach was used to obtain the pooled odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) for coffee drinkers versus never or rare drinkers. A one-stage logistic mixed-effects model with a random intercept for each study was used to estimate the dose-response relationship. Estimates were adjusted for sex, age and the main recognized risk factors for gastric cancer. RESULTS: Compared to never or rare coffee drinkers, the estimated pooled OR for coffee drinkers was 1.03 (95% CI, 0.94-1.13). When the amount of coffee intake was considered, the pooled ORs were 0.91 (95% CI, 0.81-1.03) for drinkers of 1-2 cups per day, 0.95 (95% CI, 0.82-1.10) for 3-4 cups, and 0.95 (95% CI, 0.79-1.15) for five or more cups. An OR of 1.20 (95% CI, 0.91-1.58) was found for heavy coffee drinkers (seven or more cups of caffeinated coffee per day). A positive association emerged for high coffee intake (five or more cups per day) for gastric cardia cancer only. CONCLUSIONS: These findings better quantify the previously available evidence of the absence of a relevant association between coffee consumption and gastric cancer.

Bioenergetics of Islet Preparations in a Pilot Clinical Trial of Peri-Transplant Hydroxychloroquine for Autologous Islet Transplantation.

The inflammatory response is an obstacle to success in both allogeneic and autologous islet transplantation. In autologous islet transplantation (AIT), however, the recipient is also the donor, permitting pretreatment of donor/recipient for a controlled duration prior to transplantation. We sought to exploit this feature of (AIT) by pretreating donor/recipients with chronic pancreatitis undergoing total pancreatectomy and autologous islet transplantation (TPAIT) to test the hypothesis that peri-transplant treatment with the FDA-approved anti-inflammatory hydroxychloroquine (HCQ) improves graft function. In this randomized placebo-controlled pilot clinical study, patients (n = 6) were treated with oral HCQ for 30 days prior to and 90 days after TPAIT. In vivo islet function was assessed via Mixed Meal Tolerance Testing before HCQ treatment, 6- and 12-months after surgery. In vitro islet bioenergetics were assessed at the time of transplantation via extracellular flux analysis of islet preparation samples from the clinical trial cohort and six additional patients (n = 12). Our study shows that HCQ did not alter clinical endpoints, but HCQ-treated patients showed greater spare respiratory capacity (SRC) compared to samples from control patients (P=0.028). Glycolytic metabolism of islet preparations directly correlated with stimulated C-peptide secretion both before and after TPAIT (P=0.01, R2=0.489 and P=0.03, R2=0.674, respectively), and predicted in vivo islet function better than mitochondrial metabolism of islet preps or islet equivalents infused. Overnight culture of islet preparations altered bioenergetic function, significantly decreasing SRC and maximal respiration (P<0.001). In conclusion, while HCQ did not alter clinical outcomes, it was associated with significantly increased SRC in islet preparations. Bioenergetic analyses of islet preparations suggests that culture should be avoided and that glycolysis may be a more sensitive indicator of in vivo islet function than current metrics, including islet oxygen consumption and islet equivalents infused.

Coffee consumption and colorectal cancer risk: a multicentre case-control study from Italy and Spain.

BACKGROUND: Coffee contains many bioactive substances that can play a role on colorectal cancer. Epidemiological evidence of coffee intake and colorectal cancer is, however, inconsistent. AIM: To provide further information on the risk of colorectal cancer in relation to coffee consumption. METHODS: Data derive from two companion case-control studies conducted in Italy and Spain within the European Union Project on Health Impacts of long-term exposure to disinfection by-products in Drinking Water and the Spanish Multi-Case Control study on Cancer. These included a total of 2289 incident cases with colorectal cancer and 3995 controls with information on coffee intake. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were derived from unconditional logistic regression models, adjusted for study centre, sex, age, education, smoking, and other covariates. RESULTS: Compared with never coffee drinkers, the OR was 0.99 (95% CI 0.95-1.02) for total coffee consumption. There was no significant trend in risk with dose or duration, the ORs being 0.95 (95% CI 0.72-1.25) for an amount of five or more cups per day of coffee and 0.95 (95% CI 0.75-1.19) for a duration of consumption of 50 years or longer. The OR was 1.04 (95% CI 0.87-1.25) for two or more cups per day of decaffeinated coffee. There were no heterogeneity across strata of various covariates, as well as no apparent differences between various anatomical subsites. CONCLUSION: This large pooled analysis of two studies shows no association of coffee and decaffeinated coffee with colorectal cancer risk.

Genetically predicted circulating concentrations of micronutrients and risk of colorectal cancer among individuals of European descent: a Mendelian randomization study.

BACKGROUND: The literature on associations of circulating concentrations of minerals and vitamins with risk of colorectal cancer is limited and inconsistent. Evidence from randomized controlled trials (RCTs) to support the efficacy of dietary modification or nutrient supplementation for colorectal cancer prevention is also limited. OBJECTIVES: To complement observational and RCT findings, we investigated associations of genetically predicted concentrations of 11 micronutrients (ß-carotene, calcium, copper, folate, iron, magnesium, phosphorus, selenium, vitamin B-6, vitamin B-12, and zinc) with colorectal cancer risk using Mendelian randomization (MR). METHODS: Two-sample MR was conducted using 58,221 individuals with colorectal cancer and 67,694 controls from the Genetics and Epidemiology of Colorectal Cancer Consortium, Colorectal Cancer Transdisciplinary Study, and Colon Cancer Family Registry. Inverse variance-weighted MR analyses were performed with sensitivity analyses to assess the impact of potential violations of MR assumptions. RESULTS: Nominally significant associations were noted for genetically predicted iron concentration and higher risk of colon cancer [ORs per SD (ORSD): 1.08; 95% CI: 1.00, 1.17; P value = 0.05] and similarly for proximal colon cancer, and for vitamin B-12 concentration and higher risk of colorectal cancer (ORSD: 1.12; 95% CI: 1.03, 1.21; P value = 0.01) and similarly for colon cancer. A nominally significant association was also noted for genetically predicted selenium concentration and lower risk of colon cancer (ORSD: 0.98; 95% CI: 0.96, 1.00; P value = 0.05) and similarly for distal colon cancer. These associations were robust to sensitivity analyses. Nominally significant inverse associations were observed for zinc and risk of colorectal and distal colon cancers, but sensitivity analyses could not be performed. None of these findings survived correction for multiple testing. Genetically predicted concentrations of ß-carotene, calcium, copper, folate, magnesium, phosphorus, and vitamin B-6 were not associated with disease risk. CONCLUSIONS: These results suggest possible causal associations of circulating iron and vitamin B-12 (positively) and selenium (inversely) with risk of colon cancer.

Adherence to nutrition-based cancer prevention guidelines and breast, prostate and colorectal cancer risk in the MCC-Spain case-control study.

Prostate, breast and colorectal cancer are the most common tumours in Spain. The aim of the present study was to evaluate the association between adherence to nutrition-based guidelines for cancer prevention and prostate, breast and colorectal cancer, in the MCC-Spain case-control study. A total of 1,718 colorectal, 1,343 breast and 864 prostate cancer cases and 3,431 population-based controls recruited between 2007 and 2012, were included in the present study. The World Cancer Research Fund/American Institute for Cancer Research (WCRC/AICR) score based on six recommendations for cancer prevention (on body fatness, physical activity, foods and drinks that promote weight gain, plant foods, animal foods and alcoholic drinks; score range 0-6) was constructed. We used unconditional logistic regression analysis adjusting for potential confounders. One-point increment in the WCRF/AICR score was associated with 25% (95% CI 19-30%) lower risk of colorectal, and 15% (95% CI 7-22%) lower risk of breast cancer; no association with prostate cancer was detected, except for cases with a Gleason score ≥7 (poorly differentiated/undifferentiated tumours) (OR 0.87, 95% CI 0.76-0.99). These results add to the wealth of evidence indicating that a great proportion of common cancer cases could be avoided by adopting healthy lifestyle habits.

Voriconazole MICs are predictive for the outcome of experimental disseminated scedosporiosis.

Background: Scedosporiosis is associated with a mortality rate of up to 90% in patients suffering from disseminated infections. Recommended first-line treatment is voriconazole, but epidemiological cut-off values and clinical breakpoints have not been determined. Objectives: To correlate voriconazole treatment response in mice suffering from disseminated scedosporiosis with MIC values determined using CLSI broth microdilution, Etest (bioMérieux) and disc diffusion. Methods: Voriconazole MICs for 31 Scedosporium apiospermum strains were determined using CLSI broth microdilution, Etest and disc diffusion. Groups of mice were challenged intravenously with 1 out of 16 S. apiospermum strains (voriconazole CLSI broth microdilution MIC range: 0.125-8.0 mg/L) and treated with 40 mg/kg voriconazole orally by gavage once daily. Efficacy of voriconazole was evaluated by a statistically significant ( P < 0.05) reduction in fungal burden in brain. Results: A categorical agreement of 90.4% was reached for CLSI broth microdilution and disc diffusion and of 93.6% for CLSI broth microdilution and Etest. Correlation of CLSI MICs and in vivo outcome was good, as mice challenged with strains with an MIC ≤2 mg/L responded to voriconazole therapy in 92.3% and those challenged with strains with an MIC ≥4 mg/L responded to voriconazole therapy in 33.3%. Conclusions: CLSI broth microdilution and Etest deliver comparable results that enable a prediction of in vivo outcome. Our results suggest that voriconazole is able to reduce fungal burden in the brain of 92.3% of all mice challenged with strains with voriconazole CLSI MICs ≤2 mg/L, while mice challenged with strains with CLSI MICs ≥4 mg/L showed limited response to voriconazole treatment.

Voriconazole minimum inhibitory concentrations are predictive of treatment outcome in experimental murine infections by Candida glabrata.

In this study, 27 clinical isolates of Candida glabrata with voriconazole (VRC) minimum inhibitory concentrations (MICs) ranging from ≤0.03 µg/mL to 8 µg/mL were tested to determine whether in vitro data are predictive of in vivo efficacy. The efficacy of VRC administered at 40 mg/kg was assayed in a neutropenic murine model of disseminated infection by C. glabrata. The reduction in fungal tissue burden in the kidneys was used as a marker of treatment efficacy. VRC reduced the fungal tissue burden in mice infected with strains that had MICs below the epidemiological cut-off value (ECV) of 0.25 µg/mL. Variable efficacy of VRC was obtained when the MIC equalled the ECV, and VRC was ineffective when the MIC exceeded the ECV. These results suggest that the use of in vitro data could be useful to predict the outcome for infections by this fungus.

Antifungal therapies in murine infections by Candida kefyr.

Candida kefyr is an emerging pathogen able to cause disseminated infection, especially in immunocompromised patients. Although guidelines for the treatment of invasive candidiasis have been published, no specific recommendations against C. kefyr are available. We determine the in vitro killing activity of amphotericin B (AMB), fluconazole (FLC) and caspofungin (CFG) as well as their efficacy in a murine model of systemic infection by two C. kefyr strains. Time-kill curves of AMB, FLC and CFG were determined in final volumes of 10 ml containing the assayed drugs ranged from 0.03 to 32 µg ml-1 at different time points and efficacy of the drugs was evaluated in a systemic model of candidiasis, conducted in immunosuppressed mice, through survival, (1→3)-ß-D-glucan levels in serum and fungal load in kidneys. AMB and CFG showed fungicidal and FLC fungistatic activity against both isolates. The three drugs were able to reduce fungal burden in kidneys and (1→3)-ß-D-glucan concentration in serum of infected mice, with CFG showing the highest efficacy, followed by FLC. In conclusion, CFG showed efficacy over AMB and FLC against the systemic candidiasis by C. kefyr. The established epidemiological cut-off for anidulafungin seems the best indicator of outcome for echinocandins.

Efecto de una modificación reglamentaria en la incidencia de lesiones en lucha leonesa / Rules modification effect's in incidence of injuries in lucha leonesa (leonesa wrestling)

ObjetivoConocer la incidencia de lesiones graves en la lucha leonesa y valorar el efecto en éstas de una modificación reglamentaria.Material y métodosEstudio de cohortes retrospectivas (2006–2007) y prospectivas (2008, reglamento modificado). Fueron incluidos todos los luchadores que compitieron en categoría senior (edad media 22±6,8 años) en la liga de invierno durante las temporadas 2006, 2007 y 2008. Las fuentes de información utilizadas fueron las actas de los corros, los partes de accidente y un cuestionario específico cumplimentado por entrevista dirigida a los luchadores. Se entendió como lesión grave cualquiera que se produjera durante el combate y tuviera como efecto una baja superior a 28 días. Se calculó la incidencia de lesiones graves por número de corro, luchadores, combates y caídas.ResultadosParticiparon en las tres temporadas un total de 143 luchadores varones. Se documentaron un total de 14 lesiones que afectaron a 13 luchadores. Las zonas anatómicas más afectadas fueron el hombro y la rodilla, y el tipo de lesión más frecuente observada fue el esguince, seguido de las contusiones y de las luxaciones. En el total de las temporadas estudiadas hubo una lesión grave cada 7 corros, se lesionó de gravedad uno de cada 36 luchadores y se produjo una lesión grave por cada 161 combates o 400 caídas. Se registraron 4 lesiones graves durante las temporadas 2006–2007 y ninguna durante la temporada 2008 (en la que se introdujo una modificación reglamentaria); las diferencias observadas en las incidencias no alcanzaron la significación estadística.ConclusionesLa lucha leonesa presenta una incidencia de lesiones similar a la de otros deportes de combate. El penalizar las sueltas y todas las caídas como enteras y mantener los combates a dos caídas parece ayudar a reducir la incidencia de lesiones graves. Sin embargo, se necesitan otros estudios con series temporales más largas que confirmen ese hallazgo(AU)

Aim: To determine the incidence of major injuries sustained in Leon’s wrestling and to evaluate the effect of rules modification on that incidence. Material and methods:This is a retrospective (2006–07) and prospective cohorts (2008, modified rules) study. All wrestlers (mean age 22±6,8 years) who took part in senior competition during winter seasons in 2006, 2007 and 2008, were included in the study. Data were obtained by means of competition records, accident reports and specific and personal questionnaires. Major injuries were considered when they took place while wrestling and as a result, the wrestlers were out of for more than 28 days. Incidence of major injuries was calculated with regard to the number of competitions, combats, takedowns and wrestlers.ResultsA total of 143 male wrestlers took part at least in one of the 3 seasons. 14 injuries were documented affecting to 13 wrestlers. The most frequently injured body regions were shoulder and knee, and the most frequent injuries were sprains followed by contusions and joint dislocations. In the total of analyzed seasons, a major injury was observed every 7 competitions, 161 combats and/or 400 takedowns; and one per 36 wrestlers suffered a major injury. Each of every 4 major injuries were registered during 2006 and 2007, and none during 2008, when a new rule was included. Some differences in the incidence of major injuries were observed, but none of them were statistically significant Conclusions: Leon’s wrestling shows and incidence of injuries similar to other combat sports. A reduction in the incidence of major injuries is observed when all there leases and the falls are interpreted as a ‘‘complete fall’’ and when the fight ends after two falls.However, longer studies are required in order to confirm these findings(AU)

Leptospirosis hemorrágica pulmonar / Hemorrhagic pulmonary leptospirosis

La leptospirosis es una enfermedad infecciosa característica de países orientales húmedos. La incidencia en países occidentales es relativamente infrecuente. La enfermedad suele manifestarse de dos formas clínicas principales: la hepato-renal y la pulmonar, generalmente con cierto grado de solapamiento entre ambas.Presentamos un paciente con una presentación severa de leptospirosis hemorrágica pulmonar que en el curso de la enfermedad, presentó un cuadro de embolismo multisistémico (bazo, riñón y sistema nervioso central -SNC-). (AU)